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Identification and functional analysis of the SET domain-containing gene family in Cordyceps militaris

Summary

Researchers identified 22 genes in the medicinal fungus Cordyceps militaris that control how genetic information is accessed through histone modifications. By studying how these genes respond to salt and amino acid treatments, they found that two specific genes (CmSET14 and CmSET16) are linked to cordycepin production, a compound with potential anti-cancer properties. When these genes were enhanced in the fungus, cordycepin production increased significantly, offering a new strategy to boost production of this valuable medicinal compound.

Background

SET domain-containing genes encode histone lysine methyltransferases that play important roles in fungal development, pathogenicity, secondary metabolite synthesis, and environmental stress responses. While SET genes have been studied in several model fungi, their identification and function in Cordyceps militaris, an important medicinal fungus known for cordycepin production, have not been reported.

Objective

This study aimed to identify and characterize the SET domain-containing gene family in C. militaris through genome-wide analysis, construct phylogenetic relationships with other fungal species, analyze expression patterns under salt stress and alanine treatment, and validate the functional role of selected SET genes in cordycepin biosynthesis.

Results

Twenty-two SET domain-containing genes were identified in C. militaris, distributed proportionally across seven chromosomes and classified into seven subfamilies. Phylogenetic analysis showed high homology of SETD2, Suv4-20, SET1, and SET_EZH subfamilies across the five fungi examined. CmSET14 and CmSET16 were upregulated under both salt stress and alanine treatment. Overexpression of both genes significantly enhanced cordycepin production compared to wild-type strains.

Conclusion

This study provides the first systematic identification and functional characterization of the SET gene family in C. militaris, establishing the foundation for understanding epigenetic regulation of cordycepin biosynthesis and providing insights for improving secondary metabolite production in this medicinal fungus.
  • Published in:Scientific Reports,
  • Study Type:Molecular Biology Research,
  • Source: PMID: 41083608, DOI: 10.1038/s41598-025-19513-6
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